PMID- 29242008
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Linking)
VI  - 89
DP  - 2018 May
TI  - Immune responses to peptides containing homocitrulline or citrulline in the 
      DR4-transgenic mouse model of rheumatoid arthritis.
PG  - 75-81
LID - S0896-8411(17)30581-4 [pii]
LID - 10.1016/j.jaut.2017.12.002 [doi]
AB  - Antibodies to proteins/peptides containing citrulline are hallmarks of Rheumatoid 
      Arthritis (RA). These antibodies are strongly associated with the expression of 
      the Shared Epitope (SE). RA patients also generate antibodies to 
      homocitrulline-containing proteins/peptides (also referred to as 
      anti-carbamylated protein antibodies (Anti-CarP)). This study was undertaken to 
      investigate the relationship between homocitrulline and citrulline immune 
      responses using an established mouse model of RA: DR4-transgenic (DR4tg) mice 
      that express the human SE. C57BL/6 (B6) and DR4tg (on a B6 background) mice were 
      immunized subcutaneously with a homocitrullinated peptide (HomoCitJED). Splenic T 
      cell proliferation was evaluated by (3)H-thymidine incorporation assay. 
      Antibodies to homocitrullinated and citrullinated antigens were screened by 
      enzyme-linked immunosorbent assay (ELISA). Antibody cross-reactivity was examined 
      by inhibition with HomoCitJED and its citrullinated counterpart peptide, CitJED 
      (the number of homocitrullines in HomoCitJED is equal to the number of 
      citrullines in CitJED). HomoCitJED-immunized DR4tg mice developed early T and B 
      cell responses to HomoCitJED and late responses to CitJED. These mice also 
      developed anti-CCP2 antibodies. In some mice, antibodies to HomoCitJED were also 
      reactive to CitJED. B6 mice immunized with HomoCitJED developed late T and B cell 
      responses to HomoCitJED, but did not generate responses to citrullinated 
      antigens. Unlike DR4tg mice, anti-HomoCitJED antibodies from B6 mice did not 
      react to CitJED. In conclusion, DR4tg mice immunized with HomoCitJED developed 
      immune responses to CitJED, indicating cross-reactivity. CitJED immune responses 
      were dependent on the SE. HomoCitJED responses occurred in the absence of the SE 
      (B6 mice); however, they developed earlier in DR4tg SE-expressing mice.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Lac, Patrick
AU  - Lac P
AD  - Department of Microbiology and Immunology, The University of Western Ontario, 
      London, ON, Canada.
FAU - Saunders, Sheri
AU  - Saunders S
AD  - Department of Microbiology and Immunology, The University of Western Ontario, 
      London, ON, Canada.
FAU - Tutunea-Fatan, Elena
AU  - Tutunea-Fatan E
AD  - Department of Microbiology and Immunology, The University of Western Ontario, 
      London, ON, Canada.
FAU - Barra, Lillian
AU  - Barra L
AD  - Department of Microbiology and Immunology, The University of Western Ontario, 
      London, ON, Canada; Department of Medicine/Rheumatology, The University of 
      Western Ontario, London, ON, Canada.
FAU - Bell, David A
AU  - Bell DA
AD  - Department of Medicine/Rheumatology, The University of Western Ontario, London, 
      ON, Canada.
FAU - Cairns, Ewa
AU  - Cairns E
AD  - Department of Microbiology and Immunology, The University of Western Ontario, 
      London, ON, Canada; Department of Medicine/Rheumatology, The University of 
      Western Ontario, London, ON, Canada. Electronic address: 
      ewa.cairns@schulich.uwo.ca.
LA  - eng
GR  - 133685/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171211
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Anti-Citrullinated Protein Antibodies)
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 1190-49-4 (homocitrulline)
RN  - 29VT07BGDA (Citrulline)
SB  - IM
MH  - Animals
MH  - Anti-Citrullinated Protein Antibodies/metabolism
MH  - Arthritis, Rheumatoid/*immunology
MH  - Citrulline/*analogs & derivatives/*immunology
MH  - Disease Models, Animal
MH  - Epitopes/*immunology
MH  - Female
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Immunity, Humoral
MH  - Immunization
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Peptides/*immunology
OTO - NOTNLM
OT  - Anti-citrullinated protein/peptide antibodies
OT  - Anti-homocitrullinated (carbamylated) protein/peptide antibodies
OT  - Cross-reactivity
OT  - Mouse model
OT  - Rheumatoid arthritis
OT  - Shared Epitope
EDAT- 2017/12/16 06:00
MHDA- 2019/02/26 06:00
CRDT- 2017/12/16 06:00
PHST- 2017/08/28 00:00 [received]
PHST- 2017/11/30 00:00 [revised]
PHST- 2017/12/03 00:00 [accepted]
PHST- 2017/12/16 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2017/12/16 06:00 [entrez]
AID - S0896-8411(17)30581-4 [pii]
AID - 10.1016/j.jaut.2017.12.002 [doi]
PST - ppublish
SO  - J Autoimmun. 2018 May;89:75-81. doi: 10.1016/j.jaut.2017.12.002. Epub 2017 Dec 
      11.